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Intralesional Bleomycin Combined With Cryotherapy in the Treatment of Recalcitrant Verruca Vulgaris

Verruca vulgaris is a common cutaneous manifestation of Human Papillomavirus (HPV) infection that presents as hyperkeratotic, cauliflower-like papules with central black petechiae. These lesions may be resistant to conventional therapies, posing a therapeutic challenge and prolong significant morbidity for the patient. This case report demonstrates an immediate and robust response of recalcitrant warts to intralesional bleomycin injection paired with cryotherapy.


Verruca vulgaris is a common cutaneous manifestation of human papillomavirus (HPV) infection that presents as hyperkeratotic, cauliflower-like papules with central black petechiae; it is most often found on the digits, palmoplantar, and periungual regions. These lesions may be associated with pain, social stigma, and limitations on activities of daily life. Current therapies include salicylic acid, cryotherapy, surgical removal, chemotherapeutics (eg, 5-fluorouracil, bleomycin), immunotherapies (eg, candida antigen, MMR, and HPV vaccines), photodynamic therapy, and laser treatments (eg, pulsed-dye, carbon dioxide, erbium, neodymium).1 However, lesions may be resistant to conventional methods, posing a significant therapeutic challenge. Here we present the case of a patient with recalcitrant warts unresponsive to six unique treatment modalities who exhibited complete resolution with intralesional bleomycin and cryotherapy.



A 64-year-old man presented with a three-month history of untreated warts. On exam, verrucous keratotic papules with capillary thrombosis under dermoscopy were appreciated on the left second (Figure 1A) and fifth digits. Initial attempts at cryotherapy destruction paired with daily salicylic acid 17% under occlusion were unsuccessful. Following 14 months of five treatments with cryotherapy and daily over-the-counter salicylic acid 17% with minimal response and the development of new lesions, a decision was made to administer a single treatment of cantharone and continue with salicylic acid 17%. Temporary regression of the lesions was followed by significant regrowth in the previously affected areas. Further approaches with intralesional candida antigen (0.6 ml) were determined ineffective after the third injection without response. Due to continued lack of improvement, squaric acid sensitization began with a 2% solution applied topically to the right upper arm and 0.2% administered daily and later increased to 0.625%. Around this time, the patient also received his first dose of the HPV vaccine series. However, treatment with squaric acid failed to improve the lesions and was discontinued. Subsequent daily application of 5% fluorouracil cream resulted in patient reports of increased growth and associated pain. Due to concern for the development of peripheral neuropathy, therapy was discontinued. Subsequent treatment with intralesional 5-fluorouracil (50 mg/ml) was unsuccessful after the third treatment. Following treatment failure with 6 different modalities, intralesional bleomycin was initiated (1 unit/1cc) on the left first and second digits (Figure 1A) as previous studies demonstrated efficacy in periungual and palmoplantar warts.2,3Intralesional bleomycin was delivered to 9 different locations across the hands bilaterally and yielded observable improvement after the first treatment as demonstrated by eschar formation (Figure 1B). Beginning with the fourth injection, cryotherapy was administered concomitantly with intralesional bleomycin and resulted in continued regression. Complete resolution of the warts was achieved after the fifth treatment of bleomycin (Figure 1C–G). The total injectable volume ranged from 1.0–1.5cc with treatment of individual lesions between 0.01–0.5 cc.



Common warts, while benign, are a significant cause of morbidity. Prompt treatment can greatly improve patient quality of life and daily functioning. However, a reliable method for treating palmoplantar and periungual warts remains challenging as these sites are more commonly refractory to conventional treatments.2 Though common first-line therapies including cryotherapy and salicylic acid have been shown to be efficacious, they require multiple treatments, can be painful resulting in reduced adherence to at home regimens, and demonstrate reduced cure rates compared to other treatment modalities.1,4–6

Initiating treatment with intralesional bleomycin should be considered in patients with recalcitrant lesions in order to reduce the burden of repeated clinic visits and prevent further spread of infection. Recalcitrant warts have been shown to be responsive to bleomycin by either microneedling, multi puncture, or intralesional injection.3,7–9 Bleomycin, an antitumor antibiotic derived from Streptomyces verticillus, exhibits antiviral properties by binding to DNA and causing strand scission.10 Potential side effects can include hyperpigmentation, scarring, and Raynaud’s phenomenon.9 In patients with known vasculopathies or with lesions in regions of cosmetic concern, microneedling with topical application of bleomycin may be indicated as it has been shown to reduce the incidence of these adverse reactions.7 Cryotherapy, a well-documented method for treating verruca vulgaris, demonstrates a lower efficacy when compared to intralesional bleomycin alone.11 In this case, we combined intralesional injections of bleomycin with cryotherapyollowing the third intralesional treatment and until complete response was achieved. Cryotherapy has been well documented for treating benign and malignant skin lesions, allowing for destruction of the tissue while avoiding invasive surgical paring. Additionally, the secondary numbing effect of cryotherapy may blunt the pain associated with intralesional bleomycin injection. Currently, evidence remains lacking supporting this combined treatment and further randomized control trial studies are required to characterize the efficacy of this approach in treating refractory warts. In our case, the significant response of these recalcitrant lesions may suggest that these two treatments can be used concomitantly.

Overall, this case supports the use of intralesional bleomycin coupled with cryotherapy in the treatment of recalcitrant warts as seen by the immediate and robust clinical response. In the appropriate clinical scenario, intralesional therapy may significantly decrease morbidity associated with refractory warts and provide lasting response.


All authors declare no conflicts of interest.


1. Friedman PC. Management of difficult-to-treat warts: traditional and new approaches. Am J Clin Dermatol. 2021;22(3):379-394. doi:10.1007/s40257- 020-00582-4
2. Soni P, Khandelwal K, Aara N, et al. Efficacy of intralesional bleomycin in palmo-plantar and periungual warts. J Cutan Aesthetic Surg. 2011;4(3):188- 191. doi:10.4103/0974-2077.91250
3. Barkat MT, Abdel‐Aziz RTA, Mohamed MS. Evaluation of intralesional injection of bleomycin in the treatment of plantar warts: clinical and dermoscopic evaluation. Int J Dermatol. 2018;57(12):1533-1537. doi:10.1111/ ijd.14092
4. Rivera A, Tyring SK. Therapy of cutaneous human Papillomavirus infections. Dermatol Ther. 2004;17(6):441-448. doi:10.1111/j.1396-0296.2004.04047.x
5. Lipke MM. An armamentarium of wart treatments. Clin Medicine Res. 2006;4(4):273-293. doi:10.3121/cmr.4.4.273
6. García‐Oreja S, Álvaro‐Afonso FJ, García‐Álvarez Y, et al. Topical treatment for plantar warts: A systematic review. Dermatol Ther. 2021;34(1):e14621. doi:10.1111/dth.14621
7. Kaul S, Caldito EG, Jakhar D, et al. Comparative efficacy and safety of intralesional bleomycin relative to topical bleomycin with microneedling in the treatment of warts: A systematic review. J Am Acad Dermatol. 2020;84(3):816-819. doi:10.1016/j.jaad.2020.06.035
8. Konicke K, Olasz E. Successful treatment of recalcitrant plantar warts with bleomycin and microneedling. Dermatol Surg. 2016;42(8):1007-1008. doi:10.1097/dss.0000000000000738
9. Kaul S, Kaur I, Jakhar D, et al. The diverse methods of bleomycin delivery in cutaneous warts: A literature review. Dermatol Ther. 2021;34(1):e14401. doi:10.1111/dth.14401
10. Shumer SM, O’Keefe EJ. Bleomycin in the treatment of recalcitrant warts. J Am Acad Dermatol. 1983;9(1):91-96. doi:10.1016/s0190-9622(83)70112-x
11. Dhar S, Rashid M, Islam A, Bhuiyan I. Intralesional bleomycin in the treatment of cutaneous warts: A randomized clinical trial comparing it with cryotherapy. Indian J Dermatol Venereol Leprol. 2009;75(3):262-267. doi:10.4103/0378-6323.48428



Mesgarzadeh, S., Myrdal, C., Stratton, D., & Curiel-Lewandrowski, C. (2022). Intralesional Bleomycin Combined With Cryotherapy in the Treatment of Recalcitrant Verruca Vulgaris. Journal of Drugs in Dermatology: JDD, 21(2), 195-196.


Content and images used with permission from the Journal of Drugs in Dermatology.

Adapted from original article for length and style.

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